Nanomaterials are defined as substances with particulate dimensions that are on the order of up to 0.1 μm. In the case of symmetric materials such as spherical particles, the particle diameter is the defined quantity while in the case of anisotropic materials such as rods, fibers or plates, at least one of the three axial dimensions is required to be in the defined size range.
Supercritical fluids have been used in the precipitation of fine solid particles. The phenomenon was observed and documented as early as 1879 by Hannay, J. B. and Hogarth, J., “On the Solubility of Solids in Gases,” Proc. Roy. Soc. London 1879 A29, 324, who described the precipitation of solids from supercritical fluids: “When the solid is precipitated by suddenly reducing the pressure, it is crystalline, and may be brought down as a ‘snow’ in the gas, or on the glass as a ‘frost’ . . . ”. More recently, Mohamed, R. S., et al. (1988), “Solids Formation After the Expansion of Supercritical Mixtures,” in Supercritical Fluid Science and Technology, Johnston, K. P. and Penninger, J. M. L., eds., describes the solution of the solids naphthalene and lovastatin in supercritical carbon dioxide and sudden reduction of pressure to achieve fine particles of the solute. The sudden reduction in pressure reduces the solvent power of the supercritical fluid, causing precipitation of the solute as fine particles. Tom, J. W. and Debenedetti, P. B. (1991), “Particle Formation with Supercritical Fluids—a Review,” J. Aerosol. Sci. 22:555-584, discusses rapid expansion of supercritical solutions (RESS) techniques and their applications to inorganic, organic, pharmaceutical and polymeric materials. The RESS technique is useful to precipitate small particles of shock-sensitive solids, to produce intimate mixtures of amorphous materials, to form polymeric microspheres and deposit thin films. Critical properties of common RESS solvents are provided.
Smith U.S. Pat. Nos. 4,582,731, 4,734,227 and 4,734,451, describe typical RESS processes involving rapidly releasing the pressure of a supercritical solution of a solid solute to form a film of the solute on a substrate, or to form a fine powder of the solute.
Sievers et al. U.S. Pat. No. 4,970,093 discloses a process similar to the RESS process for depositing a film on a substrate by rapidly releasing the pressure of a supercritical reaction mixture to form a vapor or aerosol which deposits a film of the desired material on a substrate. Alternatively, the supercritical fluid contains a dissolved first reagent which is contacted with a gas containing a second reagent which reacts with the first reagent to form particles of the desired material deposited as a film on the substrate.
Sievers, et al. U.S. Pat. No. 5,301,664 discloses the use of nebulizers utilizing medicaments dissolved in supercritical fluids to deliver physiologically active substances to a patient, preferably to lung tissues of the patient. The supercritical fluid process provides particles of the desired size range for administration to the patient's lungs (less than about 6.5 micrometers).
The use of supercritical co-solvents, e.g., carbon dioxide and nitrous oxide, to dissolve poorly soluble active principles is described in Donsi, G. and Reverchon, E. (1991), “Micronization by Means of Supercritical Fluids: Possibility of Application to Pharmaceutical Field, ” Pharm. Acta Helv. 66:170-173.
A modification of the RESS process is described in PCT Publication WO 90/03782 which involves dissolving a desired solid in a supercritical fluid and adding an anti-solvent which is miscible with the supercritical fluid but not with the solute in order to precipitate the solute. Such an anti-solvent process, referred to as the “gas anti-solvent” (GAS) precipitation process is also discussed in Debenedetti, P. G., et al. (1993), “Application of supercritical fluids for the production of sustained delivery devices,” J. Controlled Release 24:27-44. The GAS process is also discussed with respect to production of insulin powder in Yeo, S-D, et al. (1993), “Formation of Microparticulate Protein Powders Using a Supercritical Fluid Antisolvent,” Biotechnology and Bioengineering 41:341-346.
In most cases, usefulness of the previously disclosed rapid expansion of supercritical solutions type processes have been limited to precipitation of solutes which may be directly dissolved in the supercritical fluid, and the fine materials (particles, fibers, powders, films, etc.) generated typically have particles sizes reported to be in the range of hundreds of nanometers to several micrometers.
Sievers et al. U.S. Pat. No. 5,639,441 describes an alternative process for forming fine particles of a desired substance upon expansion of a presurized fluid, wherein the substance is first dissolved or suspended in a first fluid, which is then mixed with an immiscible second fluid and the mixture is reduced in pressure to form a gas-borne dispersion. While the disclosed process is described as increasing the range of substances which can be delivered as fine particles by rapid pressure reduction of a carrier fluid, the particles sizes obtained are still reported to be in the 0.1 to 6.5 micrometer range.
Sun et al. “Preparation of Nanoscale Semiconductors Through the Rapid Expansion of Supercritical Solution (RESS) into Liquid Solution”, Proceedings of the 5th International Symposium on Supercritical Fluids, 8-12 April, Atlanta USA (2000) describe a process comprising expansion of a supercritical ammonia/Pb(NO3)2 solution into a solution of NaS in ethanol such that nanoparticles of PbS having an average particle size of 4 nm are produced. This process is limited by the fact that it is a reactive process where the reactants have to be soluble in supercritical solutions.
Combes et al., in US Statutory Invention Registration H1,839 describes a supercritical fluid process specifically for precipitating tonor additive wax particles. While the process is generally described as resulting in particles in the size (diameter) range of from 0.001 μm-4.0 μm, the examples indicate that particles with a size of from 0.01 to 5.0 microns are obtained.
Pace et al U.S. Pat. No. 6,177,103, Bausch et al U.S. Pat. No. 6,299,906, and Kropf et al. U.S. Pat. No. 6,316,030 describe processes for generating submicron particles involving expansion of supercritical fluids wherein conventional hydrophilic/hydrophobic surface modifying agents are used. While in some instances the surface modifier may be added to the supercritical fluid prior to expansion thereof, the purpose of the surface modifier typically is to prevent agglomeration of particles after they are precipitated.
Fulton et al. U.S. Pat. Nos. 5,158,704 and 5,266,205 and Matson et al U.S. Pat. No. 5,238,671 describe supercritical fluid systems comprising a continuous nonpolar fluid phase, an immiscible polar fluid (e.g., water) phase having a solute material dissolved therein, and a surfactant, wherein the nonpolar fluid, polar fluid and surfactant intermix to form a reverse micelle system comprising dynamic aggregates of surfactant molecules surrounding a core of the polar fluid and solute material dispersed in the continuous nonpolar fluid phase. Potential applications for such systems are described as including chromatography, protein separations, solute extractions, chemical reactions as described in U.S. Pat. No. 5,238,671, and gas phase reactions wherein polar catalysts or enzymes may be molecularly dispersed in a nonpolar gas phase.
The use of supercritical CO2 has been suggested as an alternative to organic cleaning solvents, particularly in combination with reverse micelles or microemulsions, as described in Supercritical Fluid Cleaning, J. McHardy and S. Sawan, Eds., Noyes Publications, Westwood, N.J. (1998), pp. 87-120, Chapter 5, entitled “Surfactants and Microemulsions in Supercritical Fluids” by K. Jackson and J. Fulton. U.S. Pat. Nos. 5,789,505, 5,944,996, 6,131,421 and 6,228,826 describe cleaning processes employing carbon dioxide as solvent along with surfactants having CO2-philic portions and hydrophilic or otherwise CO2-phobic portions, wherein the combination of CO2 and surfactant are useful for removing CO2-phobic (including hydrophilic) contaminants from a substrate. U.S. Pat. No. 6,131,421 in particular describes the formation of a reverse micelle system useful for removing hydrophilic contaminants when water is also included with the carbon dioxide and surfactant. There is no disclosure, however, of the use of such materials in a rapid expansion process for generating fine particles of a desired material having particulate dimensions in the range of 0.5 to 10 nanometers.
U.S. Pat. No. 6,010,542 describes a method of dyeing substrates in carbon dioxide, comprising combining liquid or supercritical carbon dioxide with a dye and an amount of surfactant sufficient to solubilize, emulsify, or disperse the dye in the carbon dioxide, and then dyeing the substrate with the dye composition. There is no disclosure, however, of the use of such dispersed dye compositions in a rapid expansion process for generating fine particles of a desired material having particulate dimensions in the range of 0.5 to 10 nanometers.
PCT Publication No. WO 02/45868 A2 describes a method for the patterned deposition of a material comprising the steps of dissolving or suspending the material in a solvent phase comprising compressed carbon dioxide, and depositing the solution or suspension onto a surface, evaporation of the solvent phase leaving a patterned deposit of the material, wherein the method is described as being particularly sutable for the patterned deposition of polymers and small molecules in organic light emitting diodes and organic transistors. It is generally stated that small organic molecules, polymers and inorganic particles ranging in size from 1 nm to 1 μm can be deposited from compressed carbon dioxide, and that in some instances small amounts of surfactants such as perfluorinated polyethers can be added to aid in formation of a homogeneous solution or suspension. The examples thereof, however, in each instance describe only the deposition of carbon dioxide soluble polymers, with or without added surfactant, and there is no disclosure of the generation of fine particles of a desired material having particulate dimensions in the range of 0.5 to 10 nanometers.
U.S. Pat. No. 6,221,275 describes a process for increasing the conductivity of a liquid where crystalline materials having major dimensions of less than 100 nm are generated and dispersed by direct evaporation into a low vapor pressure liquid by heating the substance to be dispersed in a vacuum while passing a thin film of the fluid near the heated substance and cooling the fluid to control its vapor pressure. It is reported that nanocrystalline aluminum oxide produced by the process had an average grain size of less than 3 nm. There is no disclosure, however, of the use a rapid expansion process for generating nanoscale materials.
It would be desirable to provide a simple supercritical fluid/compressed liquid process for generating nanoscale particulate materials having a particulate size of less 10 nm.